A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.

In brief: Alpha-ketoglutarate is a common metabolite in the tricarboxylic acid cycle and is central in modulating the reproductive potential in animal models. The present scoping review systematically covers the spectrum of a wide range of evidence from different viewpoints, focusing on the underlying processes and mechanisms of the developmental framework, aiming to fill the gaps within the existing literature.

Abstract: Alpha-ketoglutarate is an important intermediate molecule in the tricarboxylic acid cycle with a prominent role in distinct biological processes such as cellular energy metabolism, epigenetic regulation, and signaling pathways. We conducted a registered scoping review (OSF: osf.io/b8nyt) to explore the impact of exogenous supplementation on reproductive capabilities. Our strategy included evaluating the main research literature from different databases like PubMed-MEDLINE, Web of ScienceTM, Scopus, and Excerpta Medica dataBASE using a specific systematic layout to encompass all investigations based on experimental models and critically compare the results. Twenty-one studies were included in the main body of this manuscript, which revealed that exogenous supplementation induced dose- and sex-dependent modifications. This metabolite modulates the expression of pluripotency genes, thus controlling stem cells' self-renewal, differentiation, and reprogramming dynamics, while also alleviating structural transformations induced by exposure to heavy metals and other inhibitors. This significantly demonstrated a direct influence of alpha-ketoglutarate in mitigating oxidative stress and prolonging the lifespan, consequently supporting metabolic and endocrine adjustments. It influences oocyte quality and quantity, delays reproductive aging, and establishes an optimal competence framework for development with minimal risk of failure. Therefore, alpha-ketoglutarate is linked to improving reproductive performance, but further studies are needed due to a lack of studies on humans.